Groningen Research Institute for Asthma and COPD (GRIAC)

​​​The main theme of the Groningen Research Institute for Asthma and COPD (GRIAC) is unravelling the underlying mechanisms of the development, progression and remission of airway obstruction, allergy and airway hyperresponsiveness,their mutual interactions,and their relevance to treatment.These phenomena are important risk factors for the development of asthma and COPD and crucial characteristics in their clinical pictures. Research within GRIAC takes place at the interface of fundamental and applied patient-related research.

GRIAC operates within the University Medical Center Groningen (UMCG) and its overarching research theme “Healthy Ageing”, and partially within the Groningen Research Institute of Pharmacy (GRIP), with a focus on Molecular Life and Health. Research within GRIAC focuses on the main challenges of obstructive airway and pulmonary disease:

Identifying risk factors for the development, progression and remission of disease

Unraveling the pathophysiology of allergen-, environmental- and smoke- induced disease, in humans, animal models, and in vitro cell systems

Unraveling the effects of disease-related inflammation on lung function, hyperresponsiveness and remodeling of large and small airways

Defining new targets for drug intervention and evaluation of intervention strategies

Development of noninvasive or less invasive tools to assess severity of disease and effects (and side effects) of treatment.

Scope of research

These challenges are investigated particularly in asthma and COPD, resulting in integrated subprograms on: 1. Epidemiology and genomics 2. Molecular Medicine: Pathophysiology and pathogenes is of chronic lung disease and drug target identification. 3. Clinical Medicine: Assessment, modulation of and intervention in disease severity,progression and remission

Epidemiology and genomics

The longstanding expertise in identifying risk factors and the availability of large, prospective, long-term follow up of patient-based and population-based cohorts (such as LifeLines) and the collaboration with the Department of Genetics enables extensive sub-programs, including exposomics, (epi)genome-wide association, genome-wide interactions and transcriptome sequencing studies. This has resulted in identification of numerous novel genetic loci related to asthma and COPD onset and progression. Proteomic and lipidomic research has led to identification of disease susceptibility and progression markers. GRIAC has a longstanding collaboration with the proteomics facility (Prof. R.P.H. Bisschof), and recently incorporated its first member from the European Research Institute on the Biology of Ageing (ERIBA dr. V. Guryev), strengthening its focus on bioinformatic analyses of integrated genomic datasets.

Molecular medicine

GRIAC is actively engaged in studies linking clinical outcomes to pathophysiology, also on a molecular basis. Often based on outcomes from and also involving omics studies, the functionality of genes and proteins in disease is studied using molecular approaches in cells and tissues from patients, in cell lines and in animal models. In vivo and in vitro silencing and overexpression of genes are now established techniques that are operational at the UMCG and GRIP, including the development of knock out and transgenic mouse models, and the use of RNA interference and pharmacological modulation of cells and tissue slices. Fundamental to this line of research is the exploration of intracellular and intercellular pathways and interactions relevant for tissue repair, disease development, progression and remission, as well as for the exploration of novel drug targets.

Clinical medicine

Patient-centered research is at the heart of GRIAC. Our translational research approach includes large-scale clinical management in primary care, clinical and intervention studies in allergy, food allergy, asthma and COPD. For example, a GRIAC investigator led the first large-scale intervention study of tiotropium in asthma [N Engl J Med. 2012 Sep 27;367(13):1198-207]. Because it is moving towards precision medicine in obstructive and pulmonary disease, GRIAC is in an excellent position to incorporate genomic markers in intervention studies. GRIAC is actively engaged in the development of clinical questionnaires for disease diagnosis and monitoring of disease control. Pulmonary rehabilitation and novel bronchoscopic intervention techniques are evaluated for the treatment of COPD.

Healthy aging has been adopted as the main theme for the research and clinical profile of the UMCG. An important long-term project within this theme is “LifeLines”, a planned 30-year survey on risk factors (obtained by questionnaire, objective physiological data and biological and genomic markers) for disease development; COPD and asthma are among the leading themes. We are actively participating in LifeLines, for example as members of the scientific board and the genetics committee. We are also involved in designing the study of the new generation of 1,500 babies born in LifeLines families: LifeLines NEXT.

GRIAC is involved in several symposia and training programs focused on healthy ageing, including Bronchitis IX: lungs on the edge of health and aging, a conference in the framework of the COST program on early origins of chronic lung disease and a training school on molecular mechanisms of ageing.

GRIAC has generated PhD projects explicitly focusing on healthy ageing. For example the thesis of Figarska (2014) focused on the genetics of healthy ageing. GRIAC is collaborating actively with the GUIDE program Medicinal Chemistry % Bioanalysis (MCB) and ERIBA in the area of proteogenomics (Prof. dr. Rainer Bischoff; Prof. dr. Peter Horvatovich) and Dr. Victor Guryev, principal investigator at the ERIBA institute, has joined as a member of GRIAC.

Mechanisms of tissue repair are increasingly being investigated in the context of lung function decline in COPD.

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